Katrina Dionne, Université de Montréal

Katrina Dionne1,2, Étienne Bélanger1,2, Mehdi Benlarbi1,2, Claudia Santos Saenz3, Shilei Ding2, Catherine Bourassa2, Halima Medjahed2, Geneviève Laroche3, Julie Carbonneau4, Véronique Lisi5, David Goldfarb6,7, Vincent-Philippe Lavallée5,8, Elie Haddad1,5,8, Soren Gantt1,5, Madeleine Durand2,9, Guy Boivin4, Marceline Côté3, Andrés Finzi1,2 1Département de Microbiologie, Immunologie et Infectiologie, Faculté de Médecine, Université de Montréal 2Axe Immunopathologie, Centre de Recherche du CHUM, Montréal, Québec, Canada 3Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada 4Centre de Recherche du CHU de Québec, Université de Laval, Québec, Québec, Canada 5Centre de Recherche du CHU Sainte-Justine, Université de Montréal, Montréal, QC, Canada. 6Dept of Pathology & Laboratory Medicine, BC Children's Hospital & BC Women's Hospital + Health Centre 7Clinical Professor, University of British Columbia, Vancouver, Canada 8Département de Pédiatrie, Université de Montréal, Montréal, QC H3T 1C5, Canada. 9Département de Médecine, Faculté de Médecine, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

Fighting & Responding

Context: Highly Pathogenic Avian Influenza (HPAI) outbreaks represent a serious global public health threat. H5N1 is highly transmissible and can be lethal in humans, with recent cases reported in the US and Canada, including a 13-year-old girl in British Columbia who required two months of intensive care following H5N1 infection in November 2024. Antibody responses after infection or vaccination mainly target hemagglutinin (HA) and neuraminidase (NA), generating strong neutralizing activity. These antibodies may also mediate Fc-effector functions such as antibody-dependent cellular cytotoxicity (ADCC), though this activity remains poorly characterized. Seasonal influenza vaccines target Influenza A (H1N1/H3N2) and B viruses, but their ability to elicit cross-reactive antibodies against H5Nx avian viruses is unclear. Methods: We evaluated cross-reactive antibodies responses following seasonal vaccination in healthcare workers at CHUM. Plasma was collected during the Fall 2024 influenza vaccination campaign. Antibody binding to H1N1, H3N2, and multiple H5Nx subtypes was measured by ELISA and flow cytometry. Neutralization was evaluated using pseudovirues and ADCC using stable HA/NA/HA-NA-expressing target cells. Plasma from the H5N1-infected BC teen was analyzed to assess immune responses across influenza subtypes. Results: Seasonal vaccination increased antibody levels against vaccine strains and several H5 subtypes. Cross-neutralizing and ADCC against H5Nx viruses was detected in a subset of vaccinees. Notably, plasma from the H5N1-infected teen exhibited markedly elevated responses against H5Nx strains, with a particularly potent neutralizing activity. Importance: This study highlights how seasonal vaccination shapes antibody responses against HPAI compared to infection, providing insights to better prepare ourselves for a potential future pandemic.